chr19-49011063-C-T

Variant names:

• chr19-49011063-C-T
• rs190848887
• NM_006666.3:c.852C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006666.3(RUVBL2):​c.852C>T​(p.Arg284Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000811 in 1,608,224 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (6 hom.)
• Consequence: RUVBL2 NM_006666.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96
• Publications: 0 publications found

Genes affected

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-49011063-C-T is Benign according to our data. Variant chr19-49011063-C-T is described in ClinVar as Benign. ClinVar VariationId is 709500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00463 (692/149388) while in subpopulation AFR AF = 0.0165 (670/40712). AF 95% confidence interval is 0.0154. There are 6 homozygotes in GnomAd4. There are 332 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 692 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006666.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	NM_006666.3	MANE Select	c.852C>T	p.Arg284Arg	synonymous	Exon 10 of 15	NP_006657.1	Q9Y230-1
	RUVBL2	NM_001321190.2		c.750C>T	p.Arg250Arg	synonymous	Exon 10 of 15	NP_001308119.1	B3KNL2
	RUVBL2	NM_001321191.1		c.717C>T	p.Arg239Arg	synonymous	Exon 10 of 15	NP_001308120.1	Q9Y230-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.852C>T	p.Arg284Arg	synonymous	Exon 10 of 15	ENSP00000473172.1	Q9Y230-1
	RUVBL2	ENST00000221413.10	TSL:1	n.*61C>T		non_coding_transcript_exon	Exon 10 of 15	ENSP00000221413.6	X6R2L4
	RUVBL2	ENST00000221413.10	TSL:1	n.*61C>T		3_prime_UTR	Exon 10 of 15	ENSP00000221413.6	X6R2L4

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 684 AN: 149282 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000801

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000609

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.00108 AC: 267 AN: 246530 AF XY: 0.000859

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000727

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000420 AC: 612 AN: 1458836 Hom.: 6 Cov.: 34 AF XY: 0.000379 AC XY: 275 AN XY: 725590

African (AFR) AF: 0.0150 AC: 502 AN: 33418

American (AMR) AF: 0.000717 AC: 32 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39530

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85968

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53090

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00000901 AC: 10 AN: 1110296

Other (OTH) AF: 0.000830 AC: 50 AN: 60226

GnomAD4 genome AF: 0.00463 AC: 692 AN: 149388 Hom.: 6 Cov.: 32 AF XY: 0.00456 AC XY: 332 AN XY: 72842

African (AFR) AF: 0.0165 AC: 670 AN: 40712

American (AMR) AF: 0.000800 AC: 12 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000610 AC: 3 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9958

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67488

Other (OTH) AF: 0.00143 AC: 3 AN: 2098

Alfa AF: 0.00211 Hom.: 1

Bravo AF: 0.00503

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.2
DANN	Benign	0.88
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs190848887; hg19: chr19-49514320;